DIFFERENTIAL DIAGNOSIS IN ASSESSMENT AND

MANAGEMENT OF POST-CONCUSSIVE
SYMPTOMATOLOGY

N AT H A N D . Z A S L E R , M D , D A B P M & R , F A A P M & R , F A C R M , B I M , C B I S T
FOUNDER, CMO AND CEO,
CONCUSSION CARE CENTRE OF VIRGINIA
FOUNDER AND MEDICAL DIRECTOR, TREE OF LIFE
P R O F E S S O R , A F F I L I AT E , D E P A RT M E N T O F P M & R , V C U
A S S O C I A T E P R O F E S S O R , A D J U N C T, D E P A R T M E N T O F P M & R , U V A
EMERITUS CHAIRPERSON, IBIA
VICE-CHAIRPERSON, IBIA

CONGRESO INTERNACIONAL DE NEURORREHABILITACION

DEL DAÑO CEREBRAL
2022
 LEARNING OBJECTIVES

—  Understand the numerous limita0ons regarding how

we label, diagnose, and treat persons with concussive
brain injury.
—  Review recent advances in understanding concussion
assessment, differen0al diagnosis and natural history.
—  Discuss symptoms following concussion and related
trauma0c injuries as well as persistence of same.
—  Examine “post-concussive” symptom differen0al
diagnos0c challenges.
—  Delineate factors impac0ng symptom presenta0on.
 INTRODUCTION
—  CBI is very common and makes up the vast
majority of all trauma0c brain injuries.
—  There are nomenclature issues and
defini0onal issues that make CBI research
and study comparison challenging
par0cularly as related to persistent post-
concussive symptomatology (PPCS).
—  There is no consensus methodology for CBI
neuromedical assessment or treatment.
 INTRODUCTION
—  There is no consensus on how to differen0ate
neurogenic symptoms from non-neurogenic
symptoms aNer CBI.
—  There is no agreed upon neuropsychological
tes0ng paradigm for CBI.
—  There is no neuropsychological profile
pathognomonic for CBI.
—  The e0ology of persistent symptoms aNer CBI
con0nues to be debated.
WHAT DOES CBI REALLY MEAN?
—  GCS 13-15 – variables may impact score.
—  PTA no longer than 24 hours but not necessary.
—  LOC no longer than 30 minutes but not necessary.
—  No decline in GCS below 13 from first post-
resuscita0on scoring.
—  May or may not have an amnes0c gap (RGA vs.
AGA).
—  Other acute neurological parameters in CBI:
dazing, confusion, focal neurological symptoms or
signs, postural imbalance and cogni0ve
impairments.
 FACTS ABOUT CBI
—  Accounts for about 80-90% of all trauma0c brain
injuries.
—  True incidence is unknown due to mul0ple
factors including under-repor0ng.
—  Hospital treatment rate of 1-3 per thousand
people with es0mate of 6 per thousand persons
in the general popula0on.
—  30% incidence of PCS in healthy controls – risk
of false posi0ve diagnosis is not insignificant.
 FACTS ABOUT CBI

—  More than half of all persons with CBI have no

loss of consciousness, about 25% a brief loss of
consciousness, and about 10-15% with a more
protracted loss of consciousness.
—  Males account for more than three quarters of
all pa0ents with CBI.
—  Persons with CBI typically receive treatment for
other injuries which may make interpreta0on of
persistent symptoms more challenging.

 CBI CHALLENGES
—  Some of the key challenges:
¡  No accepted defini0on – ACRM, ICD-10, DSM-5-TR,
CDC, WHO, EFNS, Sports concussion ra0ng scales.
¡  No evidence-based defini0on that is uniformly
applied in both clinical and research sefngs.
¡  No defini0on with strictly objec0ve criteria.

¡  Normal vs. abnormal acute CT – concept of

“complicated” CBI – oNen ignored in prognosis.
¡  Significant rate of misdiagnosis - both false + and -.
 PROPOSED KEY INDICATORS OF CBI

Based on a systema=c review of highest quality research:

—  Observed and documented disorienta0on or confusion
immediately aNer the event
—  Impaired balance within one day post-injury
—  Slower reac0on 0me within two days post-injury and/or
—  Impaired verbal learning and memory within 2 days aNer
injury
÷  Carney N, Ghajar J, Jagoda A, et al: Concussion Guidelines Step 1:
systema0c review of prevalent indicators. Neurosurgery.
75(S1:S3-15), 2014
 COMMON POST-CONCUSSIVE SYMPTOMS

•  Headaches.
•  Dizziness.
•  Fatigue.
•  Irritability.
•  Anxiety.
•  Depression.
•  Insomnia.
•  Cognitive impairment.
•  Tinnitus.
 POST-CONCUSSIVE CAVEATS

— FACT: a syndrome is a consistent set

of findings associated with a condi0on
with symptom linkage and coupling of
symptom resolu0on
— FACT: there is no consistency to the
signs or symptoms of concussion
— FACT: there is no symptom or set of
symptoms that are a priori diagnos0c
of CBI

 NATURAL HISTORY OF CBI

—  Neurologic and func0onal outcome of

uncomplicated CBI is generally very good.
—  Most clinically recover within 90 days.
—  Recent work suggests that physiological
dysfunc0on may outlast clinical measures of
recovery.
—  It is currently not possible to define a single
physiological 0me window for recovery.
—  There is s0ll debate regarding how to segregate
symptoms to confirm that they are in fact post-
concussive in e0ology.
 NATURAL HISTORY OF CBI

—  “Miserable minority” – those with persistence of

symptoms - cause remains debated.
—  Greater age, higher level of educa0on and male
gender do beker….high school athletes,
par0cularly girls, at greatest risk for persistent
symptoms.
—  Chronic problems generally not due to the brain
injury itself.
—  A small percentage (5% or less) may have CBI
related long term (> 1 year) problems.
 NATURAL HISTORY OF RECOVERY

— Impact of non-CBI post-trauma0c

impairments on CBI recovery
— Impact of SGIs on CBI recovery
— Impact of “diagnos0c labels”
— Impact of nocebo effects and nega0ve
expectancies
— Impact of stress
— Impact of aken0on gained by illness
 NATURAL HISTORY OF RECOVERY

— Impact of pre-injury personality on

recovery
— Impact of misakribu0on biases
— Impact of anger
— Impact of loss aversion
— Impact of resilience level
— Impact of affec0ve symptoms

 OUTCOMES AFTER CBI
—  Most evidence indicates the presence of
cogni0ve deficits in the first two weeks post-
injury.
—  Some evidence suggests that complete recovery
(implying clinical and physiological) may take 6
months or more.
—  A small number of studies indicate that CBI
increases risk of psychiatric illness and suicide.
 WHAT DEFINES PPCS?

—  There is no consistently agreed to defini0on of

the 0meframe for assigna0on of the term
“persistent” rela0ve to con0nued symptoms
following concussion.
—  In sports related concussion, PPCS has been
defined from > than 10 days to close to one
year.
—  Based on the Berlin 5th ICCS, PPCS is > than
10-14 days in adults and > than 2 months in
children.
 WHAT DEFINES PPCS?
—  In civilian CBI literature, some have used a
0meframe of 3 months, others 6 months and
yet others 12 months.
—  Persistence of symptoms following concussion
should not inherently imply the cause is the
original concussion.
¡ Makdissi, et al. BJSM. 2017; McCrory, et al.
BJSM. 2017.
 WHAT CAUSES PPCS?

—  There is a dearth of good research that addresses

symptom origin as related to “persistent
symptoms” aNer CBI.
—  Such research also needs to consider SGIs, use of
effort, symptom and performance validity tes0ng as
well as response bias measures.
—  There is a dire need for assessment algorithms to
be developed for persons with persistent
symptoms along with standardiza0on of the
medical exam.
 HOW MUCH DOES BRAIN DAMAGE ACCOUNT
FOR PERSISTENT SYMPTOMS AFTER CBI?

— Morphometric and connec0vity changes

on imaging aNer CBI cannot be assumed to
be pathognomonic for CBI related brain
sequelae.
— Structural imaging via MRI as well as
morphometric brain imaging have not
been found to be significantly associated
with greater post-CBI symptom repor0ng.
 HOW MUCH DOES BRAIN DAMAGE ACCOUNT
FOR PERSISTENT SYMPTOMS AFTER CBI?

— DTI abnormali0es are associated with

cogni0ve impairment aNer CBI –including
aken0on, memory and execu0ve func0on
(meta-analysis by Oehr et al, 2017).
— The extent to which actual brain injury
following CBI contributes to persistent
post-concussive symptoms remains
unclear and debated.
 REPORTING OF POST-CBI SYMPTOMS

—  Symptom repor0ng is individualized and represents

the summa0on of mul0ple variables including but
not limited to:
¡  Mental health history
¡  Current life stressors
¡  Neuromedical status including chronic pain
¡  Affec0ve status
¡  Characterological / personality factors
¡  Psychosocial factors
¡  Environmental factors including incen0ves vs.
disincen0ves for symptom repor0ng
 POST-CONCUSSIVE SYMPTOMS

— Controversy regarding origin of post-

concussive symptoms.
— Many types of post-concussive symptoms
are not due to the concussion itself.
— A CBI history does not mean that all post-
Injury problems are secondary to same.
— Think of the 3 Cs in the context of
differen0al diagnosis.
— PCS vs. PPCS
 THE NECK AS A CAUSE OF
CONCUSSIVE TYPE SYMPTOMS

—  Neck injuries or whiplash associated disorders are a

common comorbid finding in persons with concussion.
—  Neck injury and associated dysfunc0on of cervical
structures/systems may be a cause of and/or
compound/perpetuate PCS/PPCS (Packard; Zasler;
Evans; Leddy, among others).
—  The cervical spine is proposed to play an important role
in persistent symptoms (Ellis et al, 2015; Leslie and
CraNon, 2013; Marshall et al, 2015), but this idea is
largely unstudied.
 THE NECK AS A CAUSE OF PCS AND PPCS

—  Many authors suggest that the brain is unlikely to be the

only source of ongoing symptoms, and other contribu0ng
sources such as the cervical spine are likely contributory
(Zasler, 1996; Leddy et al, 2012; Leslie and Craton, 2013;
Makdissi et al, 2013; Marshall et al 2015; Schneider at al,
2014; Trelevean, 2017 ).
—  Consistent with this view, Ellis et al, 2015, proposed
classifying concussion into physiological (brain-related),
ves0bulo-ocular and cervicogenic post-concussion
disorders.
 THE NECK AS A CAUSE OF PCS AND PPCS

—  A recent study by Kennedy et al (2017) showed that pain

on manual segmental tes0ng appeared to be a key
feature of a cervicogenic component to PCS and that
cervical treatment appeared to benefit neck-related
persistent post-concussion symptoms.
—  Sub-occipital musculature may impact symptoms severity
and recovery due to connec0ons to the dura (i.e. via
rectus capi0s posterior minor) (Hack et al, 1995, 2004).
—  Pathology of the myodural bridge likely contributes to
PPCS (Fakhran, Qu, Alhilali, 2016).
 WE SEE WHAT WE
LOOK FOR
WE LOOK FOR WHAT
WE KNOW

GOETHE
 DIFFERENTIAL DIAGNOSIS IN CBI

— Brain injury
— Whiplash associated disorder/
cervicocephalic syndrome
— Depression
— Chronic pain disorder
— Anxiety spectrum disorders including PTSD
— Unrelated neuromedical condi0ons
— Func0onal neurologic symptom disorder
(DSM-5-TR term for conversion)
 DIFFERENTIAL DIAGNOSIS IN CBI

— Fac00ous disorder
— Symptom exaggera0on and in the extreme
malingering (the laker rare)
— Hypochondriasis
— Misakribu0on bias
— “Good old days” bias
— Diagnosis threat
— Nocebo effects/nega0ve expectancies

 TINNITUS

—  SNHL
—  Ossicular chain disrup0on
—  Perilympha0c fistula
—  Endolympha0c hydrops
—  TMJD
—  Migraine
—  Labyrinthine concussion
—  Eustachian tube dysfunc0on
—  Medica0ons side-effects (aspirin)
—  Caffeine
—  ETOH
 HEARING LOSS

—  Sensorineural hearing loss

—  Ossicular chain disrup0on
—  Perilympha0c fistula
—  Endolympha0c hydrops
—  Labyrinthine concussion
—  Eustachian tube dysfunc0on
—  Auditory verbal agnosia (pure word deafness)
—  Central hearing loss – very rare
 VERTIGO

—  BPPV
—  Migraine
—  Cervicogenic ver0go/dizziness
—  Perilympha0c fistula
—  Endolympha0c hydrops
—  Cervical vertebral soma0c dysfunc0on
—  Eustachian tube dysfunc0on
—  Central ver0go

—  Remember to clarify the complaint of “dizzy” – light headed,

imbalanced/unstable/giddy, or ver0ginous
 IMBALANCE

—  Central impairment – cerebellar / brainstem / parietal

sensory deficits
—  Ves0bular disorders
—  Visual impairments
—  Visuoves0bular impairment
—  Cervical propriocep0ve impairments secondary to WAD
—  Medica0on induced side-effects
—  Posterior circula0on impairment
—  Basilar migraine
 VISUAL COMPLAINTS

—  Accommodative insufficiency
—  Convergence insufficiency
—  Smooth pursuit deficits
—  Saccadic eye movement impairment
—  Photosensitivity
—  Cranial nerve impairments (if seen more
commonly CN IV and CN VI)

 HEADACHE

—  Cervicogenic including referred myofascial, CSD and ON

—  Tension type headache
—  Migraine
—  Medica0on induced
—  Medica0on overuse headache
—  TMJD
—  Bruxing
—  Neuri0c / neuralgic
 DYSSOMNIA

—  Affec0ve disorders – anxiety / PTSD / depression

—  Stress
—  Sleep disorders including OSA, REM motor behaviors,
circadian rhythm disorders, PLMD and RLS
—  Pain
—  Day0me napping due to altered sleep wake cycle or excessive
fa0gue
—  Medica0ons
—  Subjec0ve insomnia
—  Neurogenic insomnia
 MOOD CHANGES

—  Organic affec0ve disorders

—  Reac0ve anxiety or depression
—  PTSD
—  Pain
—  Dysomnia / insomnia
—  Neuroendocrine deficiencies
—  Medica0on induced
—  Substance use
—  Stress
 FATIGUE

—  Neurogenic secondary to concussion

—  Dysomnia / non-restora0ve sleep cycle
—  Obstruc0ve sleep apnea
—  Affec0ve disorders such as anxiety, PTSD and depression
—  Pain
—  Medica0on adverse side effects
—  Neuroendocrine issues – low thyroid
—  Post-trauma0c fibromyalgia
—  Epilepsy
—  Feigned / exaggerated
 COGNITIVE COMPLAINTS

—  Neurocogni0ve impairment
—  Affec0ve disorders
—  Pain
—  Dysomnia / insomnia
—  Neuroendocrine deficiencies
—  Medica0on induced
—  Intracranial complica0ons – hydrocephalus
—  Epilepsy
—  Feigned / exaggerated
 SMELL AND TASTE LOSS

—  Shearing of cranial nerve I at cribriform plate

—  Focal contusion of frontotemporal cor0cal olfactory
areas, piriform cortex and/or insular cortex
—  Nasal fractures
—  Medica0on induced

—  Taste loss is rare due to innerva0on – most taste

perturba0on secondary to olfactory impairment
 FACTORS TO CONSIDER IN DIFFERENTIAL
DIAGNOSIS OF CLAIMED SYMPTOMS

—  Symptom and performance validity

—  Effort
—  Response biases
—  Soma0za0on disorders
—  Symptom magnifica0on
—  Malingering/feigning
—  FNSD
—  Fac00ous disorder
 THE ROLE OF FEAR AVOIDANCE AND
CATASTROPHIZATION IN PPCS

—  There are likely biopsychosocial influences on the

dura0on of post-concussive symptomatology.
—  The fear avoidance model has been proposed as one
mechanism that may be responsible for PPCS.
—  The fear avoidance model includes issues of
catastrophizing thoughts and fear avoidance behavior.
—  There is a high correla0on between fear avoidance
behaviors and persistent symptomatology (Wijenberg
et al in 2017; Silverberg et al, 2018).
 HOW TO TREAT PPCS
—  Remember that PPCS does not reflect a single
pathophysiological process.
—  PPCS describes a constella0on of non-specific post-trauma0c
symptoms that may be linked to coexis0ng and/or
confounding pathologies….BUT NOT ALL MAY IN FACT BE
“POST-CONCUSSIVE”.
—  A mul0modal clinical assessment is crucial to op0mize
diagnos0c accuracy and iden0fy primary, secondary and
ter0ary processes.
—  Treatment should address specific pathologies as opposed to
just subjec0ve symptoms like headache, dizziness, etc.
¡  (Makdissi, Schneider, Feddermann-Demont, et al, 2017)
 CONCLUSIONS
—  Must know who person was before injury to fully
understand response to CBI and related
consequences.
—  Understand mechanisms of injury…this is cri0cal.
—  Always try and get pre-injury records.
—  Talk with corroboratory sources.
—  Know the CBI, head injury and whiplash literature.
—  Remember that every symptom following trauma
likely has at least 2-3 poten0al causes – cri0cal to
take the blinders off!

QUESTIONS AND
ANSWERS

DR. ZASLER’S EMAIL

ADDRESS:
NZASLER@CCCV-LTD.COM